GIPC mediates the generation of reactive oxygen species and the regulation of cancer cell proliferation by insulin-like growth factor-1/IGF-1R signaling

Choi, Ji Seung; Paek, A Rome; Kim, Soo Youl; You, Hye Jin

doi:10.1016/j.canlet.2010.02.007

Cited by 17 publications

(19 citation statements)

References 43 publications

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“…In contrast, GIPC are almost absent in leukemia/lymphoma cell lines and in most cases of primary kidney tumors (Kirikoshi and Katoh, 2002a). Moreover, downregulation of GIPC expression reduces pancreatic adenocarcinoma growth in vivo or cell proliferation induced by reactive oxygen species generated by IGF-1 in cancer in vitro models (Choi et al, 2010;Muders et al, 2006Muders et al, , 2009, indicating an important role of GIPC as regulator of tumor progression (Awan et al, 2002;Lee et al, 2010a). Thus, regarding the role of RGS19 as enhancer of cell proliferation (Tso et al, 2010) is also a conceivable potential role as regulator of tumor progression through its interaction with GIPC.…”

Section: Rgs19/gaipmentioning

confidence: 87%

Regulators of G-Protein-Signaling Proteins: Negative Modulators of G-Protein-Coupled Receptor Signaling

Woodard

Jardín

Berna‐Erro

et al. 2015

International Review of Cell and Molecular Biology

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Section: Rgs19/gaipmentioning

confidence: 87%

Regulators of G-Protein-Signaling Proteins: Negative Modulators of G-Protein-Coupled Receptor Signaling

Woodard

Jardín

Berna‐Erro

et al. 2015

International Review of Cell and Molecular Biology

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“…Both LPA 1 and GIPC have been implicated in cell migration [8], [17], [30]–[32], neuronal cell activity [33], [34] and cell proliferation [9], [35], [36]. GIPC has been shown to inhibit endothelial cell migration through interaction with Endoglin [37] or syndecan-4 [38], but it promotes migration of primary arterial endothelial cells [8].…”

Section: Discussionmentioning

confidence: 99%

“…Like LPA 1 , GIPC plays a key role in cell motility as GIPC (a.k.a. Synectin) knock out mice have defects in endothelial cell migration and angiogenesis [8], [9]. We therefore wondered if GIPC might interact with the PDZ binding motif of LPA 1 to regulate its activity.…”

Section: Introductionmentioning

confidence: 99%

The PDZ Protein GIPC Regulates Trafficking of the LPA1 Receptor from APPL Signaling Endosomes and Attenuates the Cell’s Response to LPA

et al. 2012

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Lysophosphatidic acid (LPA) mediates diverse cellular responses through the activation of at least six LPA receptors – LPA1–6, but the interacting proteins and signaling pathways that mediate the specificity of these receptors are largely unknown. We noticed that LPA1 contains a PDZ binding motif (SVV) identical to that present in two other proteins that interact with the PDZ protein GIPC. GIPC is involved in endocytic trafficking of several receptors including TrkA, VEGFR2, lutropin and dopamine D2 receptors. Here we show that GIPC binds directly to the PDZ binding motif of LPA1 but not that of other LPA receptors. LPA1 colocalizes and coimmunoprecipitates with GIPC and its binding partner APPL, an activator of Akt signaling found on APPL signaling endosomes. GIPC depletion by siRNA disturbed trafficking of LPA1 to EEA1 early endosomes and promoted LPA1 mediated Akt signaling, cell proliferation, and cell motility. We propose that GIPC binds LPA1 and promotes its trafficking from APPL-containing signaling endosomes to EEA1 early endosomes and thus attenuates LPA-mediated Akt signaling from APPL endosomes.

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“…GIPC1 is upregulated in human cancers, such as breast cancer, 25, 28, 29, 32 ovarian cancer 26, 28, 34 and pancreatic cancer. 25, 27, 31 GIPC1 is a cancer-associated auto-antigen, as anti-GIPC1 human monoclonal antibody was established from a breast cancer patient.…”

Section: Cancer Biology Of Gipc Family Membersmentioning

confidence: 99%

“…1, 2, 3, 4, 16, 17, 18, 19, 20, 21, 22, 23, 24 GIPCs are involved in the trafficking of various transmembrane proteins and regulate a variety of cellular processes, such as proliferation, planar cell polarity, cytokinesis and migration. Pathologies associated with the GIPCs, such as hearing loss 11, 12 and cancer, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34 are emerging topics in the medical sciences. Here, the functional proteomics, evolutionary genetics, human genetics and cancer biology of the GIPC family members will be reviewed, with a focus on recent advances and future directions.…”

Section: Introductionmentioning

confidence: 99%

Functional proteomics, human genetics and cancer biology of GIPC family members

Katoh

2013

Exp Mol Med

123

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GIPC1, GIPC2 and GIPC3 consist of GIPC homology 1 (GH1) domain, PDZ domain and GH2 domain. The regions around the GH1 and GH2 domains of GIPC1 are involved in dimerization and interaction with myosin VI (MYO6), respectively. The PDZ domain of GIPC1 is involved in interactions with transmembrane proteins [IGF1R, NTRK1, ADRB1, DRD2, TGFβR3 (transforming growth factorβ receptor type III), SDC4, SEMA4C, LRP1, NRP1, GLUT1, integrin α5 and VANGL2], cytosolic signaling regulators (APPL1 and RGS19) and viral proteins (HBc and HPV-18 E6). GIPC1 is an adaptor protein with dimerizing ability that loads PDZ ligands as cargoes for MYO6-dependent endosomal trafficking. GIPC1 is required for cell-surface expression of IGF1R and TGFβR3. GIPC1 is also required for integrin recycling during cell migration, angiogenesis and cytokinesis. On early endosomes, GIPC1 assembles receptor tyrosine kinases (RTKs) and APPL1 for activation of PI3K–AKT signaling, and G protein-coupled receptors (GPCRs) and RGS19 for attenuation of inhibitory Gα signaling. GIPC1 upregulation in breast, ovarian and pancreatic cancers promotes tumor proliferation and invasion, whereas GIPC1 downregulation in cervical cancer with human papillomavirus type 18 infection leads to resistance to cytostatic transforming growth factorβ signaling. GIPC2 is downregulated in acute lymphocytic leukemia owing to epigenetic silencing, while Gipc2 is upregulated in estrogen-induced mammary tumors. Somatic mutations of GIPC2 occur in malignant melanoma, and colorectal and ovarian cancers. Germ-line mutations of the GIPC3 or MYO6 gene cause nonsyndromic hearing loss. As GIPC proteins are involved in trafficking, signaling and recycling of RTKs, GPCRs, integrins and other transmembrane proteins, dysregulation of GIPCs results in human pathologies, such as cancer and hereditary deafness.

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GIPC mediates the generation of reactive oxygen species and the regulation of cancer cell proliferation by insulin-like growth factor-1/IGF-1R signaling

Cited by 17 publications

References 43 publications

Regulators of G-Protein-Signaling Proteins: Negative Modulators of G-Protein-Coupled Receptor Signaling

Regulators of G-Protein-Signaling Proteins: Negative Modulators of G-Protein-Coupled Receptor Signaling

The PDZ Protein GIPC Regulates Trafficking of the LPA1 Receptor from APPL Signaling Endosomes and Attenuates the Cell’s Response to LPA

Functional proteomics, human genetics and cancer biology of GIPC family members

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